Berberine alleviates nonalcoholic fatty liver induced by a high-fat diet in mice by activating SIRT3

FASEB J. 2019 Jun;33(6):7289-7300. doi: 10.1096/fj.201802316R. Epub 2019 Mar 8.


Berberine (BBR) shows promising effects in the treatment of nonalcoholic fatty liver disease (NAFLD) by influencing various metabolic aspects. Inhibition of mitochondrial β-oxidation (β-OX) participates in the pathogenesis of NAFLD. Silent mating-type information regulation 2 homolog 3 (SIRT3) has been reported to regulate mitochondrial β-OX by deacetylating its substrate, long-chain acyl-coenzyme A dehydrogenase (LCAD). This study aimed to explore whether BBR can promote mitochondrial β-OX and the role of SIRT3 as well as the mechanisms underlying the effects of BBR on hepatic lipid metabolism in mice fed a high-fat diet (HFD). BBR can significantly improve systematic and hepatic lipid metabolism in HFD-fed mice. Metabolomics analysis revealed that β-OX was inhibited in HFD-induced mice, as indicated by the reduced production of short and medium carbon chain acyl-carnitines, the activated form of free fatty acids, via β-OX, which was reversed by BBR intervention. Exploration of the mechanism found that BBR intervention reversed the down-regulation of SIRT3 and decreased the LCAD hyperacetylation level in HFD-fed mice. SIRT3 knockout (KO) mice were used to identify the role of SIRT3 in the BBR's influence of β-OX. The beneficial effects of BBR on systemic and hepatic metabolism were profoundly attenuated in KO mice. Moreover, the promotive effect of BBR on β-OX in HFD-induced mice was partially abolished in KO mice. These results suggested that BBR alleviates HFD-induced inhibition of fatty acid β-OX partly through SIRT3-mediated LCAD deacetylation, which may provide a novel mechanism and support BBR as a promising therapeutic for NAFLD.-Xu, X., Zhu, X.-P., Bai, J.-Y., Xia, P., Li, Y., Lu, Y., Li, X.-Y., Gao, X. Berberine alleviates nonalcoholic fatty liver induced by a high-fat diet in mice by activating SIRT3.

Keywords: BBR; LCAD; mitochondrial β-OX.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Acyl-CoA Dehydrogenase, Long-Chain / metabolism
  • Animals
  • Berberine / pharmacology*
  • Berberine / therapeutic use
  • Carnitine / analogs & derivatives
  • Carnitine / metabolism
  • Diet, High-Fat / adverse effects*
  • Drug Evaluation, Preclinical
  • Enzyme Activation / drug effects
  • Fatty Acids / metabolism
  • Glucose / metabolism
  • Insulin Resistance
  • Lipid Metabolism / drug effects
  • Male
  • Metabolome / drug effects*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondria, Liver / drug effects*
  • Mitochondria, Liver / enzymology
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / enzymology
  • Non-alcoholic Fatty Liver Disease / etiology
  • Non-alcoholic Fatty Liver Disease / pathology
  • Obesity / complications
  • Oxidation-Reduction
  • Protein Processing, Post-Translational
  • Sirtuin 3 / deficiency
  • Sirtuin 3 / drug effects*
  • Sirtuin 3 / physiology


  • Fatty Acids
  • Sirt3 protein, mouse
  • acylcarnitine
  • Berberine
  • Acyl-CoA Dehydrogenase, Long-Chain
  • Sirtuin 3
  • Glucose
  • Carnitine